PMID- 31739405 OWN - NLM STAT- MEDLINE DCOM- 20200408 LR - 20200408 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 22 DP - 2019 Nov 14 TI - Tricellulin Effect on Paracellular Water Transport. LID - 10.3390/ijms20225700 [doi] LID - 5700 AB - In epithelia, large amounts of water pass by transcellular and paracellular pathways, driven by the osmotic gradient built up by the movement of solutes. The transcellular pathway has been molecularly characterized by the discovery of aquaporin membrane channels. Unlike this, the existence of a paracellular pathway for water through the tight junctions (TJ) was discussed controversially for many years until two molecular components of paracellular water transport, claudin-2 and claudin-15, were identified. A main protein of the tricellular TJ (tTJ), tricellulin, was shown to be downregulated in ulcerative colitis leading to increased permeability to macromolecules. Whether or not tricellulin also regulates water transport is unknown yet. To this end, an epithelial cell line featuring properties of a tight epithelium, Madin-Darby canine kidney cells clone 7 (MDCK C7), was stably transfected with small hairpin RNA (shRNA) targeting tricellulin, a protein of the tTJ essential for the barrier against passage of solutes up to 10 kDa. Water flux was induced by osmotic gradients using mannitol or 4 and 40 kDa-dextran. Water flux in tricellulin knockdown (KD) cells was higher compared to that of vector controls, indicating a direct role of tricellulin in regulating water permeability in a tight epithelial cell line. We conclude that tricellulin increases water permeability at reduced expression. FAU - Ayala-Torres, Carlos AU - Ayala-Torres C AD - Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin Berlin, 12203 Berlin, Germany. FAU - Krug, Susanne M AU - Krug SM AUID- ORCID: 0000-0002-1293-2484 AD - Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin Berlin, 12203 Berlin, Germany. FAU - Schulzke, Jorg D AU - Schulzke JD AUID- ORCID: 0000-0001-9947-5521 AD - Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin Berlin, 12203 Berlin, Germany. FAU - Rosenthal, Rita AU - Rosenthal R AD - Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin Berlin, 12203 Berlin, Germany. FAU - Fromm, Michael AU - Fromm M AUID- ORCID: 0000-0003-4497-7983 AD - Institute of Clinical Physiology/Nutritional Medicine, Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charite-Universitatsmedizin Berlin, 12203 Berlin, Germany. LA - eng GR - GRK 2318/Deutsche Forschungsgemeinschaft/ GR - (none)/Open Access Publication Fund of the Charite - Universitatsmedizin Berlin/ PT - Journal Article DEP - 20191114 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (MARVEL Domain Containing 2 Protein) RN - 059QF0KO0R (Water) SB - IM MH - Animals MH - Biological Transport MH - Cell Line MH - Cell Membrane Permeability MH - Dogs MH - Epithelium/metabolism MH - Gene Knockdown Techniques MH - MARVEL Domain Containing 2 Protein/genetics/*metabolism MH - Madin Darby Canine Kidney Cells MH - Tight Junctions/metabolism MH - Water/*metabolism PMC - PMC6888685 OTO - NOTNLM OT - MDCK C7 cells OT - paracellular water transport OT - tight epithelium OT - tricellular tight junction OT - tricellulin COIS- The authors declare no conflict of interest. EDAT- 2019/11/20 06:00 MHDA- 2020/04/09 06:00 PMCR- 2019/11/01 CRDT- 2019/11/20 06:00 PHST- 2019/10/10 00:00 [received] PHST- 2019/11/07 00:00 [revised] PHST- 2019/11/12 00:00 [accepted] PHST- 2019/11/20 06:00 [entrez] PHST- 2019/11/20 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/11/01 00:00 [pmc-release] AID - ijms20225700 [pii] AID - ijms-20-05700 [pii] AID - 10.3390/ijms20225700 [doi] PST - epublish SO - Int J Mol Sci. 2019 Nov 14;20(22):5700. doi: 10.3390/ijms20225700.